Triethylamine → HCID 178503265, compound

HRID 724308

Reaction equation

HRID 724308 reaction equation
[CH3:1][S:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl.[NH2:27][C@@H:28]1[CH2:33][CH2:32][C@H:31]([OH:34])[CH2:30][CH2:29]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[NH3:16].[OH:34][C@@H:31]1[CH2:32][CH2:33][C@H:28]([NH:27][C:10](=[O:12])[C:9]2[CH:13]=[CH:14][CH:15]=[N:16][C:8]=2[O:7][C:6]2[CH:5]=[CH:4][C:3]([S:2][CH3:1])=[CH:18][CH:17]=2)[CH2:29][CH2:30]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 218771372-(4-Methylsulfanyl-phenoxy)-nicotinic acidHCID 178479277HCID 178479277, compound

Product 2

HCID 222AmmoniaHCID 178503265HCID 178503265, compoundYield 181.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Methylsulfanyl-phenoxy)-nicotinic acid (500 mg, 1.91 mmol) was dissolved in dimethylformamide (10 ml) and triethylamine (800 μl, 5.74 mmol) was added followed by cis-4-aminocyclohexanol hydrochloride (290 mg, 1.91 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (404 mg, 2.10 mmol) and 1-hydroxybenzotriazole (284 mg, 2.10 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was partitioned between sat. sodium bicarbonate solution (25 ml) and ethyl acetate (20 ml) and the aqueous phase was extracted with ethyl acetate (2×20 ml). The combined organic extracts were washed with water (10 ml), brine (10 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol:concentrated aqueous ammonia (97.5:2.5:0.25 changing to 97:3:0.3, by volume) to give N-(cis-4-hydroxy-cyclohexyl)-2-(4-methylsulfanyl-phenoxy)-nicotinamide (620 mg) as a white solid.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between sat. sodium bicarbonate solution (25 ml) and ethyl acetate (20 ml)
  3. extractionthe aqueous phase was extracted with ethyl acetate (2×20 ml)
  4. washThe combined organic extracts were washed with water (10 ml), brine (10 ml)
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane

Sources & evidence

ORD record
ord-d69468b24ee649bd9f4183ae2642de3b
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Linked notes

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